12 replies to this topic

[Michael]

All:
 

Trust hormone oxytocin helps old muscle work like new, study finds

By Sarah Yang, Media Relations | June 10, 2014
BERKELEY

UC Berkeley researchers have discovered that oxytocin  a hormone associated with maternal nurturing, social attachments, childbirth and sex is indispensable for healthy muscle maintenance and repair, and that in mice it declines with age [and that restoring youthful levels restores youthful muscle repair capacity -MR].

The new study, [(1) below] ... presents oxytocin as the latest treatment target for age-related muscle wasting, or sarcopenia. ...[and] the first anti-aging molecule identified that is approved by the Food and Drug Administration for clinical use in humans ... to help with labor and to control bleeding after childbirth. Clinical trials of an oxytocin nasal spray are also underway to alleviate symptoms associated with mental disorders such as autism, schizophrenia and dementia.

Unfortunately, most of the molecules discovered so far to boost tissue regeneration are also associated with cancer... said study principal investigator Irina Conboy ...  [O]xytocin... is not known to be associated with tumors or to interfere with the immune system.

Oxytocin ... is released with a warm hug, a grasped hand or a loving gaze, and it increases libido. The hormone kicks into high gear during and after childbirth, helping new mothers bond with and breastfeed their new babies. ...    [I]n mice, blood levels of oxytocin declined with age ... [and]  there are fewer receptors for oxytocin in muscle stem cells in old versus young mice. ... [W]hile oxytocin is found in both young boys and girls, it is not yet known when levels of the hormone start to decline in humans, and what levels are necessary for maintaining healthy tissues. ...

Previous research by [lead author] Elabd found that administering oxytocin helped prevent the development of osteoporosis in mice that had their ovaries removed to mimic menopause. ... To tease out oxytocins role in muscle repair, the researchers injected the hormone under the skin of old mice for four days, and then for five days more after the muscles were injured. After the nine-day treatment, they found that the muscles of the mice that had received oxytocin injections healed far better than those of a control group of mice without oxytocin. ... [A]t about 80 percent of what we saw in the young mice.



The healthy muscle tissue on the left is from a young mouse. The ability of muscle to repair itself decreases with age, as evidenced by the middle image of old muscle tissue, which shows a lower density of muscle fibers, increased scar tissue and inflammation. The addition of oxytocin to the blood of old mice rapidly rejuvenates the old muscle, as shown on the right. (Photos by Wendy Cousin and Christian Elabd, UC Berkeley)


Interestingly, giving young mice an extra boost of oxytocin did not seem to cause a significant change in muscle regeneration. ... [But] blocking the effects of oxytocin in young mice rapidly compromised their ability to repair muscle, which resembled old tissue after an injury ... [M]ice whose gene for oxytocin was disabled ... [suffered no decline in repair capacity in youth].  ... It wasn't until the mice with the disabled oxytocin gene reached adulthood that signs of premature aging began to appear. ...

[Investigator] Cousin noted that oxytocin could become a viable alternative to hormone replacement therapy as a way to combat the symptoms of both female and male aging, and for long-term health.  ... In addition to healthy muscle, oxytocin is predicted to improve bone health, and it might be important in combating obesity.

Conboy said her lab plans to examine oxytocins role in extending a healthy life in animals, and in conserving its beneficial anti-aging effects in humans. ...

Funding from the SENS Research Foundation, the National Institute on Aging and the California Institute for Regenerative Medicine helped support this research.

Note that this is work in Irina Conboy lab. Conboy is famous for heterochronic parabiosis work, which has featured several times on the List in recent months; oxytocin now appears as one of the factors potentially involved in the rejuvenating effect of young serum.

Conboy is about to start a mega-project on identifying the interactions of factors involved in the 'parabiotic effect' and their interactions with structural repair rejuvenation biotechnologies, also funded by SENS Research Foundation (note my affiliation) and with much of the hands-on work carried out by Justin Rebo (Illuminatus here at Longecity).

-Michael

1. Christian Elabd, Wendy Cousin, Pavan Upadhyayula, Robert Y. Chen, Marc S. Chooljian, Ju Li, Sunny Kung, Kevin P. Jiang  & Irina M. Conboy
Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration
 
    Nature Communications 5, Article number: 4082
    doi:10.1038/ncomms5082
 
Published 10 June 2014
http://www.nature.co...ncomms5082.html

Edited by Michael, 10 June 2014 - 11:07 PM.

[maggie67]

I am considering injecting oxycotin at 20 micro-gs subcutaneously for osteopenia/osteoporosis.Results reversing osteopenia have been encouraging.Vet supplies have this very cheaply and appear to be the same drug and manufacturer as used in humans.It also appears to get rid of belly fat.Does anyone have any info on this as I don't like the side effect profile of any of the bone drugs even the new one by Merck -odanacatib- appears to be plagued by side effect issues.

[pone11]

I am considering injecting oxycotin at 20 micro-gs subcutaneously for osteopenia/osteoporosis.Results reversing osteopenia have been encouraging.Vet supplies have this very cheaply and appear to be the same drug and manufacturer as used in humans.It also appears to get rid of belly fat.Does anyone have any info on this as I don't like the side effect profile of any of the bone drugs even the new one by Merck -odanacatib- appears to be plagued by side effect issues.

 

Do you have any citations for that?

 

Have you seen the research claiming potassium bicarb and potassium citrate have a positive effect on bone loss markers?   It's controversial and there are counter studies, but I think low doses of potassium and bicarb are 100% benign treatments.   Paleolithic diets had more than 10 grams of potassium and modern diets have less than one.   So unlikely introducing a little more potassium into diet is going to have any negative side effect, and it might have very positive effects on bone loss (although the bicarb may also play a primary role there by elevating alkaline buffers and reducing requirement to draw bicarb from bone material).

Edited by pone11, 06 March 2015 - 04:29 AM.

[pone11]

Here is full text to the study in this thread:

http://ir.nmu.org.ua....pdf?sequence=1

 

Does anyone have rough numbers on what would be the human equivalent dose of oxytocin for a human extrapolating from doses in this study?

 

Does anyone else see the strong parallels here between this oxytocin study and the GDF-11 research?   Both lines of research are from teams that started with heterochronic parabiosis and are now branching out to study specific proteins in the plasma of young people that are directly responsible for the rejuvenation effects.   See the GDF11 thread here on Longecity:

http://www.longecity...eumyo-oa-trial/

 

I will cross post this thread on that thread as well.

 

Unlike GDF11, which is still hugely expensive and does not have basic safety studies done yet, Oxytocin looks like it might be within the reach of people today, financially, and there is the suggestion of a probable safety.

 

Note that these mouse studies - both GDF11 and oxytocin - give daily injections.   It is worth pointing out that in studies where plasma is transfused from young to old mice *weekly*, that these studies *fail* to reach positive endpoints.    So it does look like the body needs constant access to the proteins.   That in turn raises long term safety questions since an older person might be forced to take this as a daily medication for life.

 

Michael, would you ever consider taking this?   I assume not given your extremely conservative approach, but given your positive comments it would be good to hear your thoughts on what research needs to happen before humans should consider oxytocin as a therapy.

 

P.S., I cannot believe this thread did not get noticed earlier.   GDF11 appears to have everyone's attention, but oxytocin is actually similar and appears much closer to being ready for primetime.

 

Edited by pone11, 06 March 2015 - 08:32 PM.

[pone11]

I am considering injecting oxycotin at 20 micro-gs subcutaneously for osteopenia/osteoporosis.Results reversing osteopenia have been encouraging.Vet supplies have this very cheaply and appear to be the same drug and manufacturer as used in humans.It also appears to get rid of belly fat.Does anyone have any info on this as I don't like the side effect profile of any of the bone drugs even the new one by Merck -odanacatib- appears to be plagued by side effect issues.

 

Can you link to the vet product supplier page that includes pricing?

[APBT]

Here is a source for Oxytocin. 

[pone11]

Here is a source for Oxytocin. 

 

That's a complete rip off.   They are buying the product wholesale and marking it up 1000% or more.

[APBT]

Veterinary oxytocin seems to be readily available but, only by Rx and in injectable form.  Here are a couple of sources:

 

http://www.valleyvet...92-00b0d0204ae5

 

http://www.drsfoster...cfm?pcatid=1440

 

[pone11]

Veterinary oxytocin seems to be readily available but, only by Rx and in injectable form.  Here are a couple of sources:

 

http://www.valleyvet...92-00b0d0204ae5

 

http://www.drsfoster...cfm?pcatid=1440

 

Does anyone know in veterinary medicines are they using a true pharmaceutical grade, or are the regulations more lenient and they can use a less rigorous grade?   The issue is purity and possible contamination by heavy metals or toxic chemicals introduced in the manufacturing process.

 

Thanks for those links.   Interesting applications described there for the application in cows....

 

And I'm not taking this, but am very curious about the economics of commonly available forms versus GDF11.   GDF11 is basically a research-only substance only available in quantity because of recombinant manufacturing for research studies.   The volume just isn't there to get cost down.   Because of the veterinary applications, it looks like oxytocin has already pushed the price down to a level that it could be more widely used once safety is established.

 

Does anyone know what is the source for the oxytocin used in veterinary applications?  Is it from a recombinant bacteria?

Edited by pone11, 07 March 2015 - 03:05 AM.

[pone11]

Here is a pharmacy that claims to supply a time-release oral preparation of oxytocin and also a sublingual version:

http://belmarpharmacy.com/oxytocin.htm

 

I cannot find pricing yet.

 

Does anyone have an opinion on how much would absorb with these two forms?    Oral oxytocin does not survive digestion so the time release product presumably gets past the stomach and then starts to time release in small intestine.   It's not clear that you want to have a slow constant dose versus a once-a-day surge of oxytocin timed to the point in energy cycle where it might get used.

[pone11]

Does anyone have a good metabolic pathway chart for hormones that shows interactions between epinephrine and oxytocin?   I read one place that epinephrine will stimulate oxytocin release, but read elsewhere that oxytocin would stimulate epinephrine.      The charts I have seen with epinephrine tend to emphasize adrenal-pituitary interactions, whereas the charts I have seen with oxytocin tend to focus on sex hormones.   Isn't there some diagram that will join these two together and show interactions between them?

[ta5]

The study that started this thread was on male mice. But, strangely, Oxytocin did not increase muscle or bone in male mice, only female mice, in this recent study:

 

Front Endocrinol (Lausanne). 2015 May 19;6:81.
Oxytocin reverses osteoporosis in a sex-dependent manner.
Beranger GE1, Djedaini M1, Battaglia S2, et al.

The increase of life expectancy has led to the increase of age-related diseases such as osteoporosis. Osteoporosis is characterized by bone weakening promoting the occurrence of fractures with defective bone regeneration. Men aged over 50 have a prevalence for osteoporosis of 20%, which is related to a decline in sex hormones occurring during andropause or surgical orchidectomy. As we previously demonstrated in a mouse model for menopause in women that treatment with the neurohypophyseal peptide hormone oxytocin (OT) normalizes body weight and prevents the development of osteoporosis, herein we addressed the effects of OT in male osteoporosis. Thus, we treated orchidectomized mice, an animal model suitable for the study of male osteoporosis, for 8 weeks with OT and then analyzed trabecular and cortical bone parameters as well as fat mass using micro-computed tomography. Orchidectomized mice displayed severe bone loss, muscle atrophy accompanied by fat mass gain as expected in andropause. Interestingly, OT treatment in male mice normalized fat mass as it did in female mice. However, although OT treatment led to a normalization of bone parameters in ovariectomized mice, this did not happen in orchidectomized mice. Moreover, loss of muscle mass was not reversed in orchidectomized mice upon OT treatment. All of these observations indicate that OT acts on fat physiology in both sexes, but in a sex specific manner with regard to bone physiology.
PMID: 26042090

[Michael]

All:

 

The study that started this thread was on male mice. But, strangely, Oxytocin did not increase muscle or bone in male mice, only female mice, in this recent study:

 

Front Endocrinol (Lausanne). 2015 May 19;6:81.
Oxytocin reverses osteoporosis in a sex-dependent manner.
Beranger GE1, Djedaini M1, Battaglia S2, et al.

 

... Men aged over 50 have a prevalence for osteoporosis of 20%, which is related to a decline in sex hormones occurring during andropause or surgical orchidectomy. As we previously demonstrated in a mouse model for menopause in women that treatment with the neurohypophyseal peptide hormone oxytocin (OT) normalizes body weight and prevents the development of osteoporosis, herein we[...] treated orchidectomized mice, an animal model suitable for the study of male osteoporosis, for 8 weeks with OT ... However, although OT treatment led to a normalization of bone parameters in ovariectomized mice, this did not happen in orchidectomized mice. Moreover, loss of muscle mass was not reversed in orchidectomized mice upon OT treatment. All of these observations indicate that OT acts on fat physiology in both sexes, but in a sex specific manner with regard to bone physiology.
PMID: 26042090

 

While I would strongly discourage self-experimentation with oxytocin (particularly for people under the age of 60), this newer study isn't even a very relevant model of most male osteoporosis, let alone of "normal" aging or age-related sarcopenia or subclinical bone loss. Conboy's study used  old (18- to 24-month-old) normally-aging mice; these mice had their testicles cut off, leading to a dramatic and sudden plunge in testosterone with no parallel in normal aging. It's not surprising that these mice suffered a dramatic fall in bone and muscle mass, and not necessarily surprising that an intervention that helps to normalize muscle regenerative function in "normal" aging doesn't counteract losses driven by orchidectomy.

 

As an additional note of caution, however, note that the two studies weren't actually even looking at the same outcome, and people seem to be jumping to conclusions about both studies. The Conboy study found that restoring oxytocin levels in the early-old mice to those found in young mice normalized the ability of satellite cells to mobilize to effect repair of muscle damage; they didn't measure, and it's not warranted to make assumptions about, its effects on age-related loss of muscle mass (which is what was measured in the orchidectomy study), or about any of the many other forms of structural degeneration that are entailed in sarcopenia and that make old muscle is disproportionately weak relative to its mass compared to young muscle. These include degeneration of neuromuscular junctions, mitochondrial DNA deletions and ensuing fiber breakage, other mitochondrial impairments, infiltration and replacement of muscle tissue with adipose and collagen, etc. Restoring the ability of satellite cells to mobilize in response to injury isn't going to deal with any of these other problems.